Institute of Integrative Traditional & Western Medicine, Lanzhou University, Lanzhou, Gansu, China.
J Pharm Pharmacol. 2013 Apr;65(4):574-81. doi: 10.1111/jphp.12022. Epub 2013 Jan 10.
rh-IFNα2a-NGR is a promising anti-tumor candidate. The aim of present study was to compare pharmacokinetics of rh-IFNα2a-NGR with rh-IFNα2a.
Pharmacokinetics and elimination were investigated after intravenous administration to mice and rats. Compared tumor and tissue distribution profiles between rh-IFNα2a-NGR and rh-IFNα2a were illustrated in the tumor transplanted mice of SP2/0 myeloma. Double antibody sandwich ELISA method was used to assess the level of both rh-IFNα2a-NGR and rh-IFNα2a in serum, tissue, bile and urine.
After a single intravenous administration, the pharmacokinetic characters of rh-IFNα2a-NGR and rh-IFNα2a were described using a two-compartment model. No significant differences were observed between the two drugs in pharmacokinetic and elimination data. However, the concentration of rh-IFNα2a-NGR in tumor was 5.34 times and 1.52 times as high as that of rh-IFNα2a at 0.5 h (P < 0.01) and 1 h. In addition, immunohistochemical stain displayed rh-IFNα2a-NGR was predominantly located in tumor vascular tissues.
rh-IFNα2a-NGR could be an agent for tumor vascular-targeting therapy and these findings provided references for further clinical study.
rh-IFNα2a-NGR 是一种很有前途的抗肿瘤候选药物。本研究旨在比较 rh-IFNα2a-NGR 与 rh-IFNα2a 的药代动力学。
通过静脉注射给药于小鼠和大鼠，研究其药代动力学和消除。比较 rh-IFNα2a-NGR 与 rh-IFNα2a 在 SP2/0 骨髓瘤移植瘤小鼠中的肿瘤和组织分布特征。采用双抗体夹心 ELISA 法检测血清、组织、胆汁和尿液中 rh-IFNα2a-NGR 和 rh-IFNα2a 的水平。
单次静脉给药后，采用二室模型描述 rh-IFNα2a-NGR 和 rh-IFNα2a 的药代动力学特征。两种药物在药代动力学和消除数据方面无显著性差异。然而，在 0.5 h（P<0.01）和 1 h 时，rh-IFNα2a-NGR 在肿瘤中的浓度分别是 rh-IFNα2a 的 5.34 倍和 1.52 倍。此外，免疫组织化学染色显示 rh-IFNα2a-NGR 主要位于肿瘤血管组织中。
rh-IFNα2a-NGR 可能是一种肿瘤血管靶向治疗药物，这些发现为进一步的临床研究提供了参考。
